课题组前期应用生物信息学方法筛选出新型多肽TKII-10，该多肽具有抑制体外新生血管活性，但抑制视网膜新生血管效果不理想。近来课题组对TKII-10多肽的氨基酸序列进行生物学特性分析计算和参数变换，实现氨基酸之间优化组合，筛选出一种抑制新生血管作用更强大和全面、氨基酸组成和理化特性更合理、半衰期延长的新型多肽UK12，其在体外可有效抑制血管内皮细胞增殖、迁移和管腔形成，在体内可抑制鸡胚尿囊膜新生血管，其抑制新生血管作用与抑制细胞内FAK活化有关。本课题将以这些发现为基础，阐明UK12抑制视网膜新生血管的作用；通过对c-Src/FAK、MAPK等信号通路检测揭示UK12多肽抑制新生血管的分子机制；并探索不同给药途径下，UK12多肽对眼部组织的通透性。通过本项目研究将有望找到一种可通过安全途径给药、有效抑制新生血管、制备简单、成本较低的潜在小分子多肽类抗新生血管药物，为其向临床转化奠定基础。

Our previous studies have successfully selected and synthesized a newly-developed peptide，named TKII-10, in a bioinformatic method, and this peptide could effectively inhibit angiogenesis in vitro. But the inhibitory effect of TKII-10 in oxygen-induced retinopathy is not significant. By analyzing the biological features of the amino acid sequences of this anti-angiogenic peptide, and carrying out multi-parameter changes to optimize the amino acid composition, our group has recently developed a new peptide, named UK12, which could inhibit VEGF-induced vascular endothelial cell proliferation, migration and tube formation in vitro, and greatly inhibit angiogenesis in chick chorioallantoic membrane in vivo. Our recent study found the UK12 peptide could inhibit VEGF-induced focal adhesion kinase phosphorylation. Based on these previous researches, this study will further elucidate the inhibitory effect of UK12 in oxygen-induced retinopathy and its specific molecular mechanism in inhibiting neovascularization, and explore the effect and permeability of UK12 into ocular tissues in non-invasive or mini-invasive drug administrating methods. Small peptides, owing to their potential efficacy, sufficient penetration capability, less toxicity, and controllable production, are ideal alternatives for ocular application. This study will develop a new peptide with highly activity in inhibiting retinal neovascularization, clear molecular mechanism, and non-invasive or mini-invasive drug administration methods. Our research will provide great foundation for the transformation of these anti-angiogenic peptides into clinically applicable drugs in treating ocular neovascular diseases.